Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates.

Non-human primates (NHPs) are precious resources for cutting-edge neuroscientific research, including large-scale viral vector-based experimentation such as optogenetics. We propose to improve surgical outcomes by enhancing the surgical preparation practices of convection-enhanced delivery (CED), which is an efficient viral vector infusion technique for large brains such as NHPs'. Here, we present both real-time and next-day MRI data of CED in the brains of ten NHPs, and we present a quantitative, inexpensive, and practical bench-side model of the in vivo CED data. Our bench-side model is composed of food coloring infused into a transparent agar phantom, and the spread of infusion is optically monitored over time. Our proposed method approximates CED infusions into the cortex, thalamus, medial temporal lobe, and caudate nucleus of NHPs, confirmed by MRI data acquired with either gadolinium-based or manganese-based contrast agents co-infused with optogenetic viral vectors. These methods and data serve to guide researchers and surgical team members in key surgical preparations for intracranial viral delivery using CED in NHPs, and thus improve expression targeting and efficacy and, as a result, reduce surgical risks.

Anatomy and Function of the Primate Entorhinal Cortex.

The entorhinal cortex (EC) is a critical element of the hippocampal formation located within the medial temporal lobe (MTL) in primates. The EC has historically received attention for being the primary mediator of cortical information going into and coming from the hippocampus proper. In this review, we highlight the significance of the EC as a major player in memory processing, along with other associated structures in the primate MTL. The complex, convergent topographies of cortical and subcortical input to the EC, combined with short-range intrinsic connectivity and the selective targeting of EC efferents to the hippocampus, provide evidence for subregional specialization and integration of information beyond what would be expected if this structure were a simple conduit of information for the hippocampus. Lesion studies of the EC provide evidence implicating this region as critical for memory and the flexible use of complex relational associations between experienced events. The physiology of this structure's constituent principal cells mirrors the complexity of its anatomy. EC neurons respond preferentially to aspects of memory-dependent paradigms including object, place, and time. EC neurons also show striking spatial representations as primates explore visual space, similar to those identified in rodents navigating physical space. In this review, we highlight the great strides that have been made toward furthering our understanding of the primate EC, and we identify paths forward for future experiments to provide additional insight into the role of this structure in learning and memory.

Medial Entorhinal Cortex Selectively Supports Temporal Coding by Hippocampal Neurons.

Recent studies have shown that hippocampal "time cells" code for sequential moments in temporally organized experiences. However, it is currently unknown whether these temporal firing patterns critically rely on upstream cortical input. Here we employ an optogenetic approach to explore the effect of large-scale inactivation of the medial entorhinal cortex on temporal, as well as spatial and object, coding by hippocampal CA1 neurons. Medial entorhinal inactivation produced a specific deficit in temporal coding in CA1 and resulted in significant impairment in memory across a temporal delay. In striking contrast, spatial and object coding remained intact. Further, we extended the scope of hippocampal phase precession to include object information relevant to memory and behavior. Overall, our work demonstrates that medial entorhinal activity plays an especially important role for CA1 in temporal coding and memory across time.